CZE is an appropriate technique for separating charged species, but lacks selectivity for neutral compounds. Alternative approaches such as microemulsion electrokinetic chromatography (MEEKC) have been developed to broaden its range of applications. Hyphenation of MEEKC with MS is an attractive perspective since it can enhance sensitivity and selectivity. The on-line coupling of MEEKC with MS, however, is not straightforward due to the low compatibility of non-volatile surfactant additives (e.g. SDS) and the commonly used API source, namely ESI. In order to hyphenate MEEKC with MS detection, the atmospheric pressure photoionization (APPI) source was investigated. Possibilities offered by the coupling of MEEKC with APPI-MS were highlighted for the complex separation of ionized and neutral compounds in both the positive and negative modes. MEEKC-APPI-MS performance, in terms of selectivity, efficiency and sensitivity was compared to CZE-ESI-MS and MEEKC-ESI-MS for the screening of doping substances (beta-blockers, central stimulants, diuretics, etc). Relevant selectivity and detectability, particularly for neutral, structurally related and isobaric compounds was demonstrated with the MEEKC-APPI-MS approach opening new avenues for CE-MS, in addition to the well-established CZE-ESI-MS technique.